By Dr. Abdelaty Shawky Assistant Professor of Pathology Hepatic Failure-4 By Dr. Abdelaty Shawky Assistant Professor of Pathology

Laboratory Evaluation of Liver Diseases

I. Investigations for hepatocyte integrity: Cytosolic hepatocellular enzymes: Serum aspartate aminotransferase (AST) Serum alanine aminotransferase (ALT)

* Aminotransferases: Usually either alanine aminotransferase (ALT) or aspartate aminotransferase (AST). These enzymes normally reside inside cells (in cytoplasm) so raised levels usually represent hepatocellular damage. ALT is more specific to the liver, as AST is also found in cardiac and skeletal muscle.

Very high levels of ALT(>1000 IU/L) suggest: autoimmune hepatitis. acute viral hepatitis (A or B). drug-induced hepatitis (e.g. paracetamol). Ischaemic liver diseases. The ratio of AST to ALT can give some extra clues to the cause: In chronic liver disease ALT >AST.

II. Investigations for Biliary excretory function: A. Substances normally secreted in bile: Serum bilirubin. Urine bilirubin. B. Plasma membrane enzymes (from damage to bile canaliculus): Serum alkaline phosphatase (ALP). Serum γ-glutamyl transpeptidase (GGT).

Gamma-glutamyltransferase (GGT) and Alkaline phosphatase (ALP) typically elevated in cholestasis. Alkaline phosphatase (ALP): increased also in bone disorders.

III. Investigations for hepatocyte function: Serum albumin. Prothrombin time. Albumin - sensitive marker of hepatic function, but not useful in the acute stages as it has a long half life (20 days). Prothrombin (INR) - sensitive marker of hepatic synthetic function.

* Further tests will also be needed to try to find out the underlying cause: Viral serology, e.g. hepatitis B and C, cytomegalovirus (CMV), Epstein-Barr virus and possibly HIV. Autoantibody screen, e.g. anti-mitochondrial antibody, anti-smooth muscle antibody and antinuclear antibody.

α-fetoprotein. Copper. α1-antitrypsin. Imaging techniques: ultrasound is noninvasive and helpful to detect structural abnormalities.

How to read abnormal liver function tests? Consider drug toxicity in all cases. Rise in bilirubin alone: Need to know if; Unconjugated hyperbilirubinaemia. Conjugated hyperbilirubinaemia.

Unconjugated: Conjugated: Haemolysis. Drugs. Gilbert's syndrome.(decreased bilirubin uptake by liver + reduced activity of conjugation due to impaired glucoronyl transferase). Crigler-Najjar syndrome. (deficiency in conjugation due to absent glucoronyl transferase). Conjugated: Dubin-Johnson syndrome.(defective bilirubin transport). Chronic liver disease, (usually associated with other liver function test (LFT) abnormalities).

2. Isolated rise in individual enzymes: for example, GGT and ALP: Isolated rise in Gamma-glutamyltransferase (GGT): This is most commonly due to alcohol abuse, or enzyme-inducing drugs. Isolated rise in Alkaline phosphatase (ALP): Third trimester of pregnancy (comes from the placenta - a normal finding). If isolated rise in ALP, consider other sources, e.g. bone. Fractures Paget's disease of bone Osteomalacia Bony metastases

Clinical Cases

Case-1 A neonate has been persistently jaundiced form birth despite aggressive phototherapy and exchange transfusions. Laboratory studies demonstrate significantly elevated unconjugated bilirubin and total absence of glucoronyl transferase activity. The neonate most likely has which one of the following condition? A. Crigler-Najjar syndrome. B. Gilbert syndrome. C. physiologic jaundice of neoborn. D. Dubin-Johnson syndrome.

Case-1 A neonate has been persistently jaundiced form birth despite aggressive phototherapy and exchange transfusions. Laboratory studies demonstrate significantly elevated unconjugated bilirubin and total absence of glucoronyl transferase activity. The neonate most likely has which one of the following condition? A. Crigler-Najjar syndrome. B. Gilbert syndrome. C. physiologic jaundice of neoborn. D. Dubin-Johnson syndrome.

Case-2 A 56-year-old alcoholic man presents to emergency department with confusion and lethargy. On physical examination, he is visibly jaundiced with ascites. Laboratory studies reveal increased prothrombin time and significantly increased serum ammonia levels. Given a significantly increased serum ammonia, which of the following physical findings might you expect to see? Asterixis. Caput medusa. Gynecomastia. Palmer erythema.

Case-2 A 56-year-old alcoholic man presents to emergency department with confusion and lethargy. On physical examination, he is visibly jaundiced with ascites. Laboratory studies reveal increased prothrombin time and significantly increased serum ammonia levels. Given a significantly increased serum ammonia, which of the following physical findings might you expect to see? Asterixis. Caput medusa. Gynecomastia. Palmer erythema.

Case-3 A. hepatitis A. B. hepatitis B. C. hepatitis C. D. hepatitis D. While on an international medical rotation you encounter a pregnant woman in a rural village in India who presents with fever, jaundice, and malaise. The patient unexpectedly died. This is the second case this month with a similar presentation. Which of the following is the most likely form of hepatitis? A. hepatitis A. B. hepatitis B. C. hepatitis C. D. hepatitis D. E. Hepatitis E.

Case-3 A. hepatitis A. B. hepatitis B. C. hepatitis C. D. hepatitis D. While on an international medical rotation you encounter a pregnant woman in a rural village in India who presents with fever, jaundice, and malaise. The patient unexpectedly died. This is the second case this month with a similar presentation. Which of the following is the most likely form of hepatitis? A. hepatitis A. B. hepatitis B. C. hepatitis C. D. hepatitis D. E. Hepatitis E.

Case-4 A 36-year-old man presents to the clinic with jaundice and right upper quadrant pain. On examination the liver is palpably enlarged. Laboratory studies demonstrate an increase in liver enzymes. Computed tomography demonstrates a single large mass in the right lobe of the liver, and serum α-fetoprotein is markedly elevated. Which of the following is likely to have contributed to the patient’s condition? A. Aflatoxin. B. Hepatitis A. C. Polyvinyl chloride. D. Tetracycline.

Case-4 A 36-year-old man presents to the clinic with jaundice and right upper quadrant pain. On examination the liver is palpably enlarged. Laboratory studies demonstrate an increase in liver enzymes. Computed tomography demonstrates a single large mass in the right lobe of the liver, and serum α-fetoprotein is markedly elevated. Which of the following is likely to have contributed to the patient’s condition? A. Aflatoxin. B. Hepatitis A. C. Polyvinyl chloride. D. Tetracycline.

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